An immune response can be induced against an almost limitless variety of substances. There are two principal types of immune responses: cell mediated responses and humoral responses. In both situations, an antigen, or foreign substance, is recognized by specific receptors on the surfaces of lymphocytes. Humoral responses are characterized by the production of antibodies specifically directed against regions of the antigen known as epitopes. Under normal circumstances, antigen recognition results in the destruction and/or removal of the antigen from the animal.
Induction of antibody (Ab) formation and of specific cellular responses is referred to as immunization even when infectious agents are not involved. Vaccination usually refers to immunization in which a suspension of infectious agents (or parts thereof) is administered to an animal to induce resistance to the disease caused by the infectious agents.
The intentional vaccination of individuals to protect against disease began in the eighteenth century with the inoculation of scrapings from persons infected with cowpox to protect against the related disease smallpox. Techniques have improved substantially since that time, leading to a decreased incidence of side effects due to reactions against contaminants in the vaccine and to the elicitation of an immunogenic response against materials not normally eliciting an immune response. These enhanced effects have been achieved by altering the antigen by attaching it to a carrier molecule, by chemical modification, and by administering it in conjunction with a vehicle increasinq the immunological response to the antigen (referred to as an adjuvant).
The most well known example of these vehicles enhancing an antigenic response is Freund's adjuvent, a water-in-oil emulsion containing tubercle bacillus, or the purified lipid component of the bacillus. The amount of antigen incorporated determines whether antibodies or a cell mediated response is elicited. A related example is aluminum hydroxide and nonpyogenic liposomal lipid A, described, for example, by Richards, et al., Vaccine 7, 505-512 (Dec. 1989).
Liposomes have also been used for encapsulation and administration of antigens, for example, as described by Richards, et al., "Development of liposomes as carriers for a human malaria peptide vaccine" in Liposomes as Drug Carriers ed. B. Gregoriadis pp. 235-241 (John Wiley & Sons Ltd. 1988). Although enhancing the immunological response, probably by targeting the antigen to the lymphocytes which phagocytize the liposomes and allowing the administration of higher doses of antigen and adjuvant, the problems with using liposomes and vesicles as delivery devices are manifold. They are difficult to prepare, unstable, and can only be used for encapsulation of certain types of materials.
Many infectious agents have proven difficult, if not impossible, to elicit an immunological response to that is effective in preventing subsequent infection by the agent. An example of such an agent is the human immunodeficiency virus. Other agents, such as toxins and agents used in biological and chemical warfare, are not immunogenic in the form to which a person or other animal would be exposed.
It is therefore an object of the present invention to provide a composition and method to administer antigens for immunization of an animal.
It is a further object of the present invention to provide a composition and method to effect or enhance immunization of an animal against an antigen that does not normally produce a good immunological response.
It is another object of the present invention to provide a composition, and method of use thereof, for immunization of an animal against an antigen that is easy to prepare and stable for an extended period of time prior to use and in vivo.